The envelope glycoproteins and major non-glycosylated structural proteins of squirrel monkey retrovirus and Mason-Pfizer monkey virus were demonstrated to possess common antigen determinants. While the major internal antigens of type C oncornaviruses failed to cross-react with analogous type D virus structural proteins, immunological cross-reactivity was demonstrated between the envelope glycoproteins of several type C and type D viruses of primate origin. These findings indicate that type C and type D oncornaviruses represent two evolutionarily distinct groups of viruses and raise the possibility that their shared envelope glycoprotein antigenic determinants may be a result of genetic recombination. Naturally occurring antibodies reactive with purified type D oncornavirus structural proteins were demonstrated in sera of several normal rhesus monkeys with known prior exposure to Mason-Pfizer monkey virus infected animals. The specificity of this reactivity was established by absorption with purified viral protein. This observation, in combination with the previous inability to detect full complements of Mason-Pfizer monkey virus genetic sequences in the cellular DNA of normal rhesus monkeys, provides evidence for horizontal transmission of Mason-Pfizer monkey virus.